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M Kanno

Publications and source records attributed to M Kanno.

At least 19 recordsLinked to original sources
PubMed1996

Structural differences in the ability of lysophospholipids to inhibit endothelium-dependent hyperpolarization by acetylcholine in rat mesenteric arteries.

The effects of different lysophospholipids on endothelium-dependent hyperpolarization by acetylcholine were examined in rat mesenteric arteries. Lysophosphatidylcholine with 14 or longer carbon acyl chain significantly inhibited the hyperpolarization, while that with 12 or lesser carbon acyl chain was without effect. Lysophosphatidylcholine with unsaturated acyl chain also showed a potent inhibition. Lysophosphatidylinositol and lyso-platelet activating factor, but not phosphatidylcholine, lysophosphatidic acid, lysophosphatidylethanolamine or lysophosphatidylserine, suppressed the hyperpolarization. These results suggest that the length of the carbon acyl chain and the size of the polar head group may be crucial for the effects of lysophospholipids on endothelium-dependent hyperpolarization. Accumulation of these lysophospholipids may play an important role in endothelial dysfunction associated with atherosclerosis.

Acetylcholine↗
PubMed1996

In vitro assessment for vascular selectivity of a new dihydropyridine derivative, NB-818.

The vascular selectivity of NB-818 (isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine -3, 5-dicarboxylate), a newly synthesized dihydropyridine derivative, was evaluated in in vitro experiments. NB-818 and nifedipine concentration dependently caused a relaxant effect in rabbit femoral arteries precontracted with 60 mM K+, a negative inotropic effect in guinea-pig papillary muscles, and a negative chronotropic effect in guinea-pig right atria. The onset of these inhibitory effects of NB-818 was much slower than that of nifedipine when compared at concentrations producing the same inhibition. The relaxant effect of NB-818 was about 10 times more potent than that of nifedipine, while the negative inotropic effect of NB-818 was about 100 times less potent than that of nifedipine. As a result, NB-818 showed about 300 times higher vascular selectivity than nifedipine. The two drugs exhibited a similar potency for the negative chronotropic effect. In a whole-cell configuration with voltage clamp, the blocking effect of NB-818 on L-type Ca2+ current (ICa) in guinea-pig ventricular cells appeared much more slowly than that of nifedipine and was hardly washed out. The potency of NB-818 to block ICa was markedly enhanced under depolarized conditions (i.e. at a holding potential of -30 mV) compared to that under polarized conditions (i.e. at a holding potential of -70 mV). Such a voltage-dependent blocking action on ICa was less pronounced for nifedipine. These results indicate that NB-818 is a slow-acting Ca2+ channel antagonist with much high vascular selectivity. Its vascular selectivity may be at least in part related to the marked voltage-dependent inhibition of ICa.

Animals↗
PubMed1996

Influences of the physical parameters on the risk to neck injuries in low impact speed rear-end collisions.

The current state of neck injuries sustained in car-to-car rear-end collisions were investigated according to recent automobile accident statistical data in Japan. To clarify the neck injury mechanisms for low impact speed car collisions, the newly developed impact sled experiment which simulates actual car impact acceleration was performed using human subjects. In order to measure and analyze the physical parameters such as human head rotational acceleration, neck bending moment, shearing and axial forces, the component measurement method with six-degrees of freedom was applied and demonstrated. Furthermore, relationships among the physical parameters, impact speeds, sitting positions, headrest heights and neck muscle tones applied on the subject's head and neck system were analyzed. These analyses would enable us to comprehend the conditions of the neck muscle tone and the effects of the sitting postures including headrest height, factors which are of vital importance to the understanding of neck injury mechanisms.

Acceleration↗
PubMed1996

Alpha 1-adrenoceptor subtypes mediating inotropic and electrophysiological effects in mammalian myocardium.

Stimulation of alpha 1-adrenoceptors produces a positive inotropic effect in rat and rabbit ventricular myocardium via different mechanisms, the prolongation of action potential duration (APD) exclusively in the former and an increase in myofibrillar Ca2+ sensitivity in large part in the latter. This study was designed to determine whether the two inotropic mechanisms are mediated by different alpha 1-adrenoceptor subtypes. In rat papillary muscles, the positive inotropic effect and APD prolongation induced by phenylephrine (in the presence of propranolol) were inhibited by WB-4101, but not affected by chlorethylclonidine (CEC). WB-4101, but not CEC, blocked the phenylephrine-induced inhibition of the transient outward current (Ito) in rat ventricular cells. On the other hand, WB-4101 and CEC each antagonized the positive inotropic effect of phenylephrine in rabbit papillary muscles. However, the phenylephrine-induced APD prolongation observed in rabbit papillary muscles was blocked only by WB-4101. These results indicate that the WB-4101 sensitive alpha 1-adrenoceptor subtype mediates the positive inotropism that is correlated with the APD prolongation resulting from Ito reduction, whereas the CEC-sensitive subtype mediates the positive inotropism that is probably associated with increased myofibrillar Ca2+ sensitivity. Radioligand binding studies with [3H] prazosin showed a similar ratio of alpha 1A-to alpha 1B-adrenoceptor subtypes in rat and rabbit ventricular myocardium, implying that the different degree of contribution of each action mechanism to the overall inotropic effect in the two species cannot be explained by distribution of the alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Agonists↗
PubMed1996

A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton.

Segment identity in both invertebrates and vertebrates is conferred by spatially restricted distribution of homeotic gene products. In Drosophila, the expression of Homeobox genes during embryogenesis is initially induced by segmentation gene products and then maintained by Polycomb group and Trithorax group gene products. Polycomb group gene homologs are conserved in vertebrates. Murine mel-18 and closely related bmi-1 are homologous to posterior sex combs and suppressor two of zeste. Mel-18 protein mediates a transcriptional repression via direct binding to specific DNA sequences. To gain further insight into the function of Mel-18, we have inactivated the mel-18 locus by homologous recombination. Mice lacking mel-18 survive to birth and die around 4 weeks after birth after exhibiting strong growth retardation. Similar to the Drosophila posterior sex combs mutant, posterior transformations of the axial skeleton were reproducibly observed in mel-18 mutants. The homeotic transformations were correlated with ectopic expression of Homeobox cluster genes along the anteroposterior axis in the developing paraxial mesoderm. Surprisingly, mel-18-deficient phenotypes are reminiscent of bmi-1 mutants. These results indicate that the vertebrate Polycomb group genes mel-18 and bmi-1, like Drosophila Polycomb group gene products, might play a crucial role in maintaining the silent state of Homeobox gene expression during paraxial mesoderm development.

Animals↗
PubMed1996

[Evaluation of preoperative chemotherapy for colorectal cancer].

Patients who underwent curative resection for colorectal cancer between January 1987 and June 1989 were divided into two groups, to assess the usefulness of preoperative chemotherapy (400 mg UFT therapy daily for 10 days more) and to analyze changes in the proliferative activity of tumor cells. Fifty-five cases were included in the study. Thirty-three had received no preoperative chemotherapy (Group A), and 22 had received the preoperative chemotherapy (group B). The five-year cumulative survival rate was 81.1% for group A and 90.2% for Group B. The proportion of patients with no recurrence was 75.7% in Group A and 85.7% in Group B. Both parameters thus tended to be better in patients who had received preoperative chemotherapy. When PCNA labeling before UFT therapy was compared with that after UFT therapy in 13 cases, the PCNA labeling rate decreased after UFT therapy in 9 (69%) of the 13 cases. These results suggest that preoperative chemotherapy using UFT is useful in treating colorectal cancer, and that the proliferative activity of colorectal cancer can sometimes be reduced by such preoperative adjuvant therapy.

Administration, Oral↗
PubMed1996

Alpha 1-adrenoceptor subtype distribution and the coupling to phosphoinositide hydrolysis in rat and rabbit ventricular myocardium.

The relative contributions of the alpha 1A- and alpha 1B-adrenoceptor subtypes to the stimulation of phosphoinositide (PI) hydrolysis in rat and rabbit ventricular myocardium were defined pharmacologically using WB-4101 and chloroethylclonidine (CEC). Radioligand binding experiments with [3H]prazosin showed that the maximum number of alpha 1A-adrenoceptors in rat myocardium was about ten times higher than in rabbit myocardium. The proportion of the two [3H]prazosin binding sites with high and low affinity for WB-4101 was similar in the two species: approximately 30% of the alpha 1-adrenoceptor population was pharmacologically alpha 1A and approximately 70% was alpha 1B. Phenylephrine produced concentration-dependent stimulation of PI hydrolysis in rat ventricular strips as measured by [3H]inositol monophosphate accumulation, but this stimulation was much less in rabbit. In both of the two species, WB-4101 was very effective in inhibiting phenylephrine-stimulated PI hydrolysis, whereas CEC had a minimal effect. Altogether, the degree of PI hydrolysis appears to be determined by the density of myocardial alpha 1-adrenoceptors. However, despite the greater density of the alpha 1B-subtype, it is the alpha 1A-subtype that is mainly coupled to PI hydrolysis in mammalian myocardium.

Adrenergic alpha-Agonists↗
PubMed1995

mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity.

The mammalian mel-18/bmi-1 gene products share an amino acid sequence and a secondary structure, including a RING-finger motif, with the Drosophila Polycomb group (PcG) gene products Psc and Su(z)2, implying that they represent a gene family with related functions. As Drosophila PcG gene products are thought to function as transcriptional repressors by modifying chromatin structure, Mel-18/Bmi-1 might be expected to have similar activities. Here we have analyzed the function of mel-18 and found that Mel-18 acts as a transcriptional repressor via its target DNA sequence, 5'-GACTNGACT-3'. Interestingly, this binding sequence is found within regulatory or non-coding regions of various genes, including the c-myc, bcl-2 and Hox genes, suggesting diverse functions of mel-18 as the mammalian homolog of the PcG gene. We also demonstrate that mel-18 has tumor suppressor activity, in contrast to bmi-1, which has been defined as a proto-oncogene.

3T3 Cells↗
PubMed1995

Phorbol esters elicit Ca(2+)-dependent delayed contractions in diabetic rat aorta.

To determine whether diabetes alters vascular effects mediated by activation of protein kinase C, the contractions induced by phorbol esters were examined in aortic rings from rats with 8- to 12-weeks streptozotocin-induced diabetes and compared with those from age-matched control rats. In diabetic rat aorta, phorbol 12,13-dibutyrate (PDB) (> or = 30 nM) and 12-O-tetradecanoylphorbol 13-acetate (TPA) (300 nM) elicited a delayed, sharply developing rise in tension following an initial gradually developing contraction. In control rat aorta, these agents produced only an initial slowly developing contraction. Both the initial and the delayed contractile responses observed in diabetic aorta were completely abolished by pretreatment with 20 nM staurosporine, and the delayed phase of contraction was not seen in Ca(2+)-free medium or in the presence of 1 microM nifedipine. The concentration-response curves for the contractions induced by PDB revealed that PDB at concentrations > or = 30 nM produced significantly greater responses in diabetic aorta than in control aorta. In control aorta, exposure to Ca(2+)-free medium and pretreatment with 1 microM nifedipine shifted the concentration-response curves for PDB to the right without changing the maximal response. Under these conditions, there were no differences in the curves for PDB in control and diabetic aortas. These results suggest that the appearance of the delayed phase of contraction, possibly due to a delayed opening of Ca2+ channels, during activation of protein kinase C may be responsible for the enhanced contractile responses to phorbol esters in diabetic rat aorta.

Alkaloids↗
PubMed1995

Endothelin-1 does not phosphorylate phospholamban and troponin I in intact beating rat hearts.

To determine a role of phosphorylation of specific cardiac regulatory proteins in the positive inotropic effect of endothelin-1, we examined phosphorylation of sarcoplasmic reticulum and myofibrillar proteins in perfused beating rat hearts treated with endothelin-1. In parallel experiments, the effects of isoprenaline and phorbol-12,13-dibutyrate (PDB) on protein phosphorylation were also tested. In 32Pi-labeled hearts, perfusion with isoprenaline (100 nM) caused 4.4- and 10.4-fold increases in the degree of phosphorylation of phospholamban in sarcoplasmic reticulum and of troponin I in myofibrils, respectively. In contrast, neither endothelin-1 (100 nM) nor PDB (1 microM) significantly changed the phosphorylation state of these proteins. These findings provide evidence that phosphorylation of major cardiac regulatory proteins is not responsible for the positive inotropic action of endothelin-1.

Animals↗
PubMed1995

Prognostic factors associated with differentiated thyroid cancer.

A multivariate analysis was conducted on the survival data of 180 patients who underwent curative resection for differentiated thyroid cancer between 1966 and 1987, and the 10- and 20-year survival rates were found to be 80.6% and 73.1%, respectively. A survival analysis was also performed, testing the following factors: the patient's age at the time of diagnosis, tumor size, extraglandular extension, nodal status, distant metastases, operative procedure, sex, and histology. A univariate analysis found the initial six factors to be significant prognostic variables, but the latter two to be of no significance. On the other hand, the multivariate analysis showed that distant metastases, age, and tumor size were the most significant prognosticators. Thus, the age of the patient should be taken into consideration during the follow-up of treatment for differentiated thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed1995

Case report of a patient with multiple lesions of the stomach, including multiple cancers and an adenomatous polyp.

This paper describes an unusual case of an 80-year-old man followed up for multifocal gastric cancers. There were three separate polypoid carcinomas and one adenomatous polyp with no sign of malignancy. We measured the DNA content of the gastric cancer and adenomatous cells obtained from endoscopically biopsied specimens. The adenomatous polyp and one of the cancerous lesions showed DNA diploidy. The other two cancerous lesions showed DNA aneuploidy, with different DNA index (DI) values (1.12 and 1.64, respectively). It is considered that the three cancers arose from different stem lines. However, an operation was not performed because the patient refused gastrectomy, and therefore only conservative follow up has been continued. Presentation of this case is followed by a detailed discussion focusing on the possible development of carcinoma in gastric adenomatous polyps in view of the data from the literature.

Adenomatous Polyps↗
PubMed1995

TCR repertoire in early fetal mouse thymus.

We investigated the rearrangement and expression of TCR genes in mouse fetal thymus organ culture, a system that avoids subsequent entry of hematopoietic precursor cells. The first observable rearranged TCR gene was homogeneous V gamma 2-J gamma 2, detectable as early as fetal day 11 (d11) in the thymic primordia. The productive TCR was homogeneous V gamma 5-J gamma 1, first detectable in d13 thymocytes, followed by adult-type TCR gamma (V gamma 4 and V gamma 7). Sequence analysis of TCR revealed five types of V-J junctional sequences. In the very early stage, a homogeneous V-J junction is generated via a short homology sequence in the coding region (Type I), while a short homology sequence in the P-nucleotide rather than the coding region is used in the following stage (Type II). In the later embryonic stages, diverse V-J junctions are generated by well-known mechanisms, such as P-nucleotide (Type III), N-region insertion (Type IV) or trimming of the coding ends (Type V). These findings suggest that the generation of homogeneous TCR gamma (V gamma 2 and V gamma 5) in the early fetal stages is due to the intrinsic rearrangement mechanisms and is in stage specific manner.

Animals↗
PubMed1995

Renal function in patients with high serum fluoride concentrations after prolonged sevoflurane anesthesia.

BACKGROUND: In studies of methoxyflurane-induced nephrotoxicity, renal-concentrating impairment has been observed only when serum inorganic fluoride concentrations exceed 50 microM. Prolonged sevoflurane anesthesia can result in serum inorganic fluoride concentrations in excess of 50 microM. The authors compared renal function after prolonged sevoflurane anesthesia with that after isoflurane anesthesia. In addition, they measured urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a sensitive index of renal tubular damage, during the 3-day period after anesthesia. METHODS: Thirty-four healthy patients who underwent either sevoflurane (23 patients) or isoflurane (11 patients) anesthesia at a total gas flow of 61/min for orthopedic surgery scheduled to last at least 5 h were studied. At 16.5 h after cessation of anesthesia, patients were administered 10 units of vasopressin and urine was collected frequently thereafter for evaluation of urinary osmolality. In addition, urinary excretion of NAG was measured before and on days 1-3 after anesthesia. Based on whether peak fluoride concentrations exceeded 50 microM, 23 patients anesthetized with sevoflurane were assigned to a sevofluranehigh group (> 50 microM) or a sevofluranelow (< 50 microM) group. RESULTS: The eight patients in the sevofluranehigh group had a mean peak fluoride concentration of 57.5 +/- 4.3 microM. A significant, albeit weak, inverse correlation was found between peak fluoride concentration and maximal urinary osmolality after the injection of vasopressin (r = -0.42, P < 0.05). Mean maximum urinary osmolality tended to be lower in the sevofluranehigh group (681 +/- 60 mOsm/kg) than in the other two groups after administration of vasopressin, although the difference among the three groups did not quite reach a statistical significance (P = 0.068). One patient had a transient concentrating defect (maximum urinary osmolality = 390 mOsm/kg) on day 1 after anesthesia. Urinary excretion of NAG in both the sevofluranehigh and sevofluranelow groups was greater on days 2 and 3 after anesthesia than before anesthesia. The increase in urinary NAG excretion was dose related with sevoflurane, but there was no difference in results of routine laboratory renal tests on days 2 and 3 after anesthesia among the three groups. CONCLUSIONS: The authors concluded that sevoflurane anesthesia results in increased serum fluoride concentration, a tendency toward decreased maximal ability to concentrate urine, and increased excretion of NAG. However, the increase in urinary NAG excretion was not indicative of clinically significant renal damage in these patients with no preexisting renal disease.

Acetylglucosaminidase↗
PubMed1995

Cyclic GMP-mediated inhibition of L-type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells.

1. Effects of atrial natriuretic peptide (ANP) on the L-type Ca2+ channels were examined in rabbit isolated ventricular cells by use of whole-cell and cell-attached configurations of the patch clamp methods. ANP produced a concentration-dependent decrease (10-100 nM) in amplitude of a basal Ca2+ channel current. 2. The inactive ANP (methionine-oxidized ANP, 30 nM) failed to decrease the current. 3. 8-Bromo-cyclic GMP (300 microM), a potent activator of cyclic GMP-dependent protein kinase (PKG), produced the same effects on the basal Ca2+ channel current as those produced by ANP. The cyclic GMP-induced inhibition of the Ca2+ channel current was still evoked in the presence of 1-isobutyl-3-methyl-xanthine, an inhibitor of phosphodiesterase. ANP failed to produce inhibition of the Ca2+ channel current in the presence of 8-bromo-cyclic GMP. 4. In the single channel recording, ANP and 8-bromo-cyclic GMP also inhibited the activities of the L-type Ca2+ channels. Both agents decreased the open probability (NPo) without affecting the unit amplitude. 5. The present results suggest that ANP inhibits the cardiac L-type Ca2+ channel activity through the intracellular production of cyclic GMP and then activation of PKG.

1-Methyl-3-isobutylxanthine↗